The today experimental data give us a reason to propose that in the case of the block of angiotensineconverting enzyme (ACE) and AT₁ – receptors to angiotensin II (A-II), prorenin and renin can show their profibrotic activity, acting through a specific prorenin/renin receptor. The profibrotic effect of prorenin/renin, even though mostly is noticed in the renal tissue, can cot be considered an isolated pathophysiological phenomena and P/R can connect with specific receptors on the surface of cardiomiocyte. At the present time take placethers clinical investigations of a new agent, which is the only representative of the direct inhibitors group of renin-aliskiren, which recently was approved by the FDA committee in USA as a medicine for arterial hypertension treatment. However, until present time it is not clear how much is the clinical significant is the blockade of (pro) renin receptors in accordance with the renal and cardiac fibrosis. The data of previous clinical investigations of aliskiren are very inspiring: the microalbumine level during its use decreases on 61% as compared with 50% during the ramipril intake. At present time take place two clinical investigations of the III phase on the evaluating the efficiency of aliskiren treatment in patients with chronic kidney disease (CKD): AVOID (Aliskiren in the Evaluation of Proteinuria in Diabetes) and AZTITUDE (Aliskiren Trial in Type 2 Diabetic Nephropathy). The results of these investigations should give new information on the therapy influence of aliskiren on the frequency and severityof diabetes. In such way, the opening of new mechanisms of functioning and meaning of renin – angiotensin- aldosterone system, probably shortly will have new ways of innovating reno- and cardioprotective therapy.

Our current understanding of initial pathogenetic steps in IgA nephropathy (IgAN) provides relatively limited rationale for immunosuppressive therapy. However, it is conceivable that immunosuppressive drugs might affect secondary inflammatory events triggered by glomerular immune deposits or even proteinuria per se. Some but not all randomized clinical trials on either corticosteroid monotherapy, mycophenolate mofetil monotherapy or immunosuppressive combination therapy have provided evidence for a benefit on either surrogate parameters such as proteinuria or hard end points such as renal failure. The central problem of these studies is that most were designed in the 1980s or 90s, when recommendations for supportive therapy were strikingly different from those of today. In the meantime an equal number of randomized clinical studies reporting a benefit of supportive therapy only has been published in patients with IgAN and, unfortunately, no head-to-head comparison of these two approaches is currently available. Several ongoing clinical trials may help to resolve this dilemma. Until the data of such studies become available, a pragmatic approach is to first optimize supportive therapy and reserve immunosuppressive medication for those patients failing a supportive approach and remaining at risk for progressive loss of renal function.

The main cause of death in patients with chronic kidney disease in cardiac illnesses, with the risk of their development increasing even at the low decrease levels of glomerular filtration. The cause of that could be the damage of nonexcretorial function of the kidney, one of which is decrease of the synthesis in the tubules of the active form of vitamin D (VD) – 1,25(OH)₂ - vitamin D – calcitriol, which besides regulating the phosphorus-calcium exchange has a great impact on various organs and tissues, including the cardiac system. In this review we discussed the results of clinical and experimental data, which proves that VD slows down the activity of the renin-angiotensin system, modulates the immune system, which in itself leads to a system inflammatory reaction, inhibits proliferation and helps in cell differentiation. This mechanisms lead to the atherosclerosis progression, left ventricular hypertrophy, arterial hypertension, cardiac insufficiency decrease and are in the base of better patients, receiving vitamin D therapy, survival.

In the review were evaluated the modern ways on pathogenesis of calcium nephrolythiasis from the position of the various changes of physic-chemical parameters, such as amount, volume of intake and excreted fluid, the enhancement of the urine with certain salts, top metastability etc. The data on the action of such natural inhibitors of crystallization such as citrate, magnesium, phitat, pyrophosphate, which were viewed as perspective methods of prophylaxis of recurrence of urinary kidney disease were stated.

The main causes of chronic inflammation in chronic hemodyalisis (HD) patients with end stage renal disease (ESRD) are described. The chronic inflammation factors, connected with hemodyalisis therapy in itself, as well as factors not related to hemodialysis are described. The connection between «uremic malnutrition» in chronic HD patients and chronic inflammation is shown in detail. In hemodyalisis patients with severe «uremic malnutrition» has a higher level of the main inflammation markers, than patients with no malnutrition signs. As a result of the fact that in chronic inflammation the active impact on the metabolism have anti-inflammatory cytokines, a proposition was made that chronic imflamation in hemodyalisis patients is one of the cause factors for the development of «uremic malnutrition» in this group of patients. Theoretically these interconnections seem very logical, although the results of the investigations in relation with chronic inflammation and the degree of «uremic malnutrition» in ESRD seem contradictory. The presence of this contradictions necessitate in further investigation in this direction.

In this review were analyzed the factors, helping in crystallization of calcium oxalate in renal tubules, and their role in pathogenesis of urinary kidney disease. The basic statements on the about the interactions of crystals with the epithelial renal tubular cells. For the role for the possible candidates for crystal connecting molecules were viewed sialic acid, osteopontin, phosphatidilserin, protein, connected with nucleolin, annexin II and hyaluronan, which, probably, is the main inductor of crystallization. Was supported the opinion, according to which the initiating moment of crystallization is renal epithelial damage of various genesis.

THE AIM of the investigation to evaluate the role of the system of arterial natriuretic peptides in pathogenesis of hemorrhagic fever with renal syndrome (HFRS). PATIENTS AND METHODS. The investigated group included 32 male patients of the age of 16 to 56 years old with severe and moderately severe flow of HFRS without concomitant renal pathology, cardiac and endocrine system. The control group included 12 patients and correlated with the observed group by gender, age and medical history. The concentration of natriuretic peptide 1-28 (ANP 1-28) in blood was determined by immunoferment method with the Peninsula (USA) test system after previous extraction. For the determination of the amount of N-terminal arterial natriuretic propeptide 1-98 (NT-proASP 1-98) in blood we used immunoferment kit EIA for NT-proANP Biomedica (Austria). The statistic evaluation was made with the use of the standard kit of programs Statistica 7,0. We used median, percentile, maximal and minimal values of the data, Mann –Whitney method, the Spearman rank correlation method. RESULTS. During oliguremic, polyuremic and early reconvalescent period in patients with severe form of HFRS was noticed a statistically significant decrease in the concentration of ANP 1-28 in comparison with the control group. In patients with moderate flow of HFRS in polyuremic and early reconvalescent period the concentration for this peptide is significantly lower than in control group. The minimal values of ANP 1-28 was registered in polyuremic period of the disease. In patients with the moderately severe form of the HFRS is noted statistically significant increase of the prohormone level in plasma only in polyuremic period. The maximal values of NT-proANP 1-98 wereregistered in polyuremic period of the disease. CONCLUSION. In patients with HFRS in noted the decrease in concentration of ANP 1-28 in blood, with the most expression in polyuremic period of the desease, and the increase of the level of NT-proANP 1-98 with the maximal values in polyuremic period of HFRS.

THE AIM. To investigate the activity of free radical processes in alcoholic patients (A), associated with renal damage (A with RD), and the role of depression of effectiveness of regulatory mechanisms, restricting the accumulation of high toxicity products of free radical lipid oxidation (FrLO), in the formation of the nephropathy in these patients. PATIENTS AND METHODS. Were evaluated 57 male patients (mean age of 31 ± 2,8 years), suffering from A during 5-10 years and admitted to the hospital in the state of urgent alcohol abstinence. The renal damage was discovered in 17 (29,8 %) patients. The control group included 20 healthy patients. The activity of FrLO and antioxidant defense was studied. RESULTS. In patients A the values of studied features, showing the activity of FrLO, were statistically higher than those in the healthy group patients. In these patients was discovered the depression of the first and second line mechanisms of AOD. Showed deviation was more obvious in the group of patients A with RD. CONCLUSION. The activation of FrLO developing on the phone of AOD depression, probably, played a role in the development of nephropathy in A patients.

THE AIM of the investigation was to analyze the course of combined microbe-inflammatory diseases of organs of the urogenital system in pregnant adolescents. MATERIALS AND METHODS. The course of the disease of organs of the urogenital system in 32 patients received by hospital for examination and treatment with threatened termination has been analyzed. By the results of the clinical and laboratory indexes and the microbiological examination the activity of microbe-inflammatory processes has been assessed in the organs of the urogenital system. RESULTS. Gestational pyelonephritis 34% is diagnosed at 20-23 weeks of pregnancy, acute gestational pyelonephritis in 75% cases. 32 patients had pregnancy with threatened termination: threatened miscarriage in 68.5%, threatened abortion in 12.5%, imminent miscarriage 9%, imminent premature labor 3%, incomplete out-of-hospital miscarriage 3%. Gynecological associated pathology was identified in 65% cases with predominance of candida colpitis 47%, urogenital ureaplasmosis 38%, urogenital mycoplasmosis 33%, bacterial vaginosis 9.5%. In the etiology of gestational pyelonephritis bacteria of the family Enterobacteriaceae dominated: E.coli 41%, Klebsiella spp 20%, Proteus spp 16%; more rarely Staphiloccocus spp 4%, Candida spp - 8.5% were screened. Termination of pregnancy (curettage of uterine cavity) was identified in 7 adolescents out of 32 (21%). CONCLUSION. High frequency of combined microbe-inflammatory diseases of organs of the urogenital system has been identified: gestational pyelonephritis with threatened termination of pregnancy in 100%, gynecological associated pathology in 65%. Special features of the course of gestational pyelonephritis in pregnant adolescents have been shown.

THE AIM. To study the influence of the depth of the invasion and degree of the differentiation of the tumor processes on the level of matrix-metalloproteas 2 and 9 in the urine of the patients with urinary bladder cancer. PATIENTS AND METHODS. 71 patients with urinary bladder cancer were evaluated. The comparison group consisted of 14 patients with chronic cystitis, and the control group consisted of 45 patients, without any urinary bladder problems, obstruction and infection of urinary tract. The level of metaloproteas was determined with the cymography method. RESULTS. Was proven that the proteolisis ferments of urine MMP-2 and MMP-9 are high sensitive characteristics of the presence of urinary bladder cancer, and their concentration depends on the depth of the invasion and differentiation stage of the tumor and shows it’s prognosis on the diseases flow. CONCLUSION. For the diagnostics and noninvasive determination of the depth of the invasion and the stage of the differentiation of the urinary bladder cancer it is reasonable to determine the levels of MMP-2 and MMP-9 in the urine by cymography method.

THE AIM. The goal of present investigation was to study the expression of Ki-67, p53 and bcl-2 antigens and their connection with clinic-morphological characteristics of the tumor, and also the clinical flow of the disease. PATIENTS AND METHODS. The materials of the clinical investigation of 16 patients with transitional cellular carcinoma of the urinary bladder was retrospectively studied. Immunohystochemical reaction with Ki-67, p53 and bcl-2 antibodies took place. The received histological and immunohystochemical data was co-analyzed with the follow-up results after the patients during 5 years. RESULTS. The high level of proliferative activity of the transitional cell carcinoma correlated with the lower differentiation stage of the tumor tissue (r=0,70; p=0,003) and shorter period of recurrence absence (r=0,67; p=0,078). For the carcinomas with the higher number of p-53 positive nucleae was more characteristic the lower stage of the differentiation (r=0,47; p=0,067), faster recurrence (r=72; p=0,068) and lower life duration of the patients (r=0,72; p=0,087). The apoptosis activity increased with the decrease of the differentiation stage of the tumor (r=0,67; p=0,04). Was discorered a positive correlation between tumor cell proliferation and apoptosis failure (r=0,67; p=0,04). CONCLUSION. As a result of the conducted experiment we stated that investigated antigens have a prognostic value, as a result of their close connection with the stage differentiation of the transitional cell carcinoma. Besides that the hyper expression of p53 protein was interconnected with the speed of the tumor recurrence and survival of the patients.

THE AIM. Nephrolythiasis – is a chronic disease, which is characterized by the presence of concrements in the tissues or cameras of the kidneys. The formation of the calculi is a result of complex difficult substance exchange disorders. The most common are solid crystal like calculi, which are composed of organic and non-organic salts – urates, oxalates, phosphates, carbonates, cystin, ksantin, etc. Nephrolythiasis is often concomitant with inflammation of renal tissue and system. So we thought reasonable to study the chemical components of the concrements in chronic calculous nephrolythiasis. PATIENTS AND METHODS. 584 patients, living in Varna area (Bulgaria), with examination at the St. Martin Hospital of the Medical University of Prof. Paraskev Stoyanov during the six years with the main or concomitant diagnosis of calculous pyelonephritis were investigated. The chemical components of the concrements were defined with the use of the «Urinary calculi analysis», Merk USA test. RESULTS. Pure oxalate calculi were discovered in 39 cases, pure phosphate in 34 cases. The combine concrements were noted in 443 patents. With that the calculi, which consisted of calcium oxalate with the phosphate mixture were noted in 175 patients, calcium oxalate with the urate mixture in 152 and calcium oxalate with carbonate mixture in 94 patients. CONCLUSION. The determination of the chemical compounds of the renal calculi is very important in the context of modern tendencies of preventive medicine

The Liddle syndrome was described in 1963. And according to the modern views is a tubolopathy with autosomal dominant inheritance. It is determined by the mutation of the genes, controlling the expression of β and γ-subunits of epithelial sodium channels (ENaC), which are mostly located on the apical membranes of the main cells connecting tubules and cortical collecting ducts. The disease is very rare and shows itself in a volume-dependant, low rennin hypertension, hypokaliemia, and metabolic alkolosis. The Liddle syndrome quite often manifestoes in the childhood, but can be primary noticed in adults even in elderly patients. As a treatment organic salts in the ration, potassium salt substitutive therapy and potassium saving diuretics (amylorid, triamteren) are used.

The discoverer Dr Stamen Grigorov (1878-1945) studies the natural sciences in Montpellier (France) and afterwards – medicine in Geneva (Switzerland), where he graduated in 1905. After systematic examinations of the Bulgarian yoghourt in 1905, he isolated the agent of souring, which is called in his honour. He receives for this discovery an honorary diploma and awards by Geneva University and Luis Pastcur Institute. He declines offers about leader’s work in Geneva and Sao Paolo (Brazil), he returns to Bulgaria and works as a district and head doctor at hospital in Tran. During the Balkan and First World War conlributed to the struggle against the cholera and he is awarded with military cross and Golden Red Cross. He created in his antituberculosis vaccine that used at Carlo Forlanini Institute in Rome (1935).